1. An Overview of Radiation Therapy for Health Care Professionals American Society for Radiation Oncology

2. Introduction Radiation has been an effective tool for treating cancer for more than 100 years Radiation has been an effective tool for treating cancer for more than 100 years More than 60 percent of patients diagnosed with cancer will receive radiation therapy as part of their treatment More than 60 percent of patients diagnosed with cancer will receive radiation therapy as part of their treatment Radiation oncologists are cancer specialists who manage the care of cancer patients with radiation for either cure or palliation Radiation oncologists are cancer specialists who manage the care of cancer patients with radiation for either cure or palliation Patient being treated with modern radiation therapy equipment.

3. Overview What is the physical and biological basis for radiation What is the physical and biological basis for radiation What are the clinical applications of radiation in the management of cancer What are the clinical applications of radiation in the management of cancer What is the process for treatment What is the process for treatment Simulation Simulation Treatment planning Treatment planning Delivery of radiation Delivery of radiation What types of radiation are available What types of radiation are available Summary Summary

4. Sources of Ionizing Radiation Photons Photons Gamma Rays Gamma Rays Emitted from a nucleus of a radioactive atom Emitted from a nucleus of a radioactive atom –Cobalt treatment machine –Radioisotopes used in brachytherapy X-rays X-rays Generated by a linear accelerator when accelerated electrons hit a target Generated by a linear accelerator when accelerated electrons hit a target Particle Beams Particle Beams Protons Protons Neutrons Neutrons Electrons Electrons Most external beam radiation treatments use photons generated by a linear accelerator. Source: Varian Medical Systems Inc.

5. What Is the Biologic Basis for Radiation Therapy? Radiation therapy works by damaging the DNA of cells and destroys their ability to reproduce Radiation therapy works by damaging the DNA of cells and destroys their ability to reproduce Both normal and cancer cells can be affected by radiation, but cancer cells have generally impaired ability to repair this damage, leading to cell death Both normal and cancer cells can be affected by radiation, but cancer cells have generally impaired ability to repair this damage, leading to cell death All tissues have a tolerance level, or maximum dose, beyond which irreparable damage may occur All tissues have a tolerance level, or maximum dose, beyond which irreparable damage may occur

6. Fractionation: A Basic Radiobiologic Principle Fractionation, or dividing the total dose into small daily fractions over several weeks, takes advantage of differential repair abilities of normal and malignant tissues Fractionation, or dividing the total dose into small daily fractions over several weeks, takes advantage of differential repair abilities of normal and malignant tissues Fractionation spares normal tissue through repair and repopulation while increasing damage to tumor cells through redistribution and reoxygenation Fractionation spares normal tissue through repair and repopulation while increasing damage to tumor cells through redistribution and reoxygenation

7. The Four R’s of Radiobiology Four major factors are believed to affect tissue’s response to fractionated radiation: Four major factors are believed to affect tissue’s response to fractionated radiation: Repair of sublethal damage to cells between fractions caused by radiation Repair of sublethal damage to cells between fractions caused by radiation Repopulation or regrowth of cells between fractions Repopulation or regrowth of cells between fractions Redistribution of cells into radiosensitive phases of cell cycle Redistribution of cells into radiosensitive phases of cell cycle Reoxygenation of hypoxic cells to make them more sensitive to radiation Reoxygenation of hypoxic cells to make them more sensitive to radiation

8. Clinical Uses for Radiation Therapy Therapeutic radiation serves two major functions Therapeutic radiation serves two major functions To cure cancer To cure cancer Destroy tumors that have not spread Destroy tumors that have not spread Kill residual microscopic disease left after surgery or chemotherapy Kill residual microscopic disease left after surgery or chemotherapy To reduce or palliate symptoms To reduce or palliate symptoms Shrink tumors affecting quality of life, e.g., a lung tumor causing shortness of breath Shrink tumors affecting quality of life, e.g., a lung tumor causing shortness of breath Alleviate pain or neurologic symptoms by reducing the size of a tumor Alleviate pain or neurologic symptoms by reducing the size of a tumor External beam radiation treatments are usually scheduled five days a week and continue for one to ten weeks

9. Radiation Therapy in Multidisciplinary Care Radiation therapy plays a major role in the management of many common cancers either alone or as an adjuvant therapy with surgery and chemotherapy Radiation therapy plays a major role in the management of many common cancers either alone or as an adjuvant therapy with surgery and chemotherapy Sites commonly treated include breast, prostate, lung, colorectal, pancreas, esophagus, head and neck, brain, skin, gynecologic, lymphomas, bladder cancers and sarcomas Sites commonly treated include breast, prostate, lung, colorectal, pancreas, esophagus, head and neck, brain, skin, gynecologic, lymphomas, bladder cancers and sarcomas Radiation is also frequently used to treat brain and bone metastases as well as cord compression Radiation is also frequently used to treat brain and bone metastases as well as cord compression

10. Radiation Therapy Basics The delivery of external beam radiation treatments is painless and usually scheduled five days a week for one to ten weeks The delivery of external beam radiation treatments is painless and usually scheduled five days a week for one to ten weeks The effects of radiation therapy are cumulative with most significant side effects occurring near the end of the treatment course. The effects of radiation therapy are cumulative with most significant side effects occurring near the end of the treatment course. Side effects usually resolve over the course of a few weeks Side effects usually resolve over the course of a few weeks There is a slight risk that radiation may cause a secondary cancer many years after treatment, but the risk is outweighed by the potential for curative treatment with radiation therapy There is a slight risk that radiation may cause a secondary cancer many years after treatment, but the risk is outweighed by the potential for curative treatment with radiation therapy {Sabin Motwani will send us image of mild skin redness after RT in a treatment field}. Example of erythroderma after several weeks of radiotherapy with moist desquamation Source: sarahscancerjourney.blogspot.com

11. Common Radiation Side Effects Side effects during the treatment vary depending on site of the treatment and affect the tissues in radiation field: Breast – swelling, skin redness Breast – swelling, skin redness Abdomen – nausea, vomiting, diarrhea Abdomen – nausea, vomiting, diarrhea Chest – cough, shortness of breath, esophogeal irritation Chest – cough, shortness of breath, esophogeal irritation Head and neck – taste alterations, dry mouth, mucositis, skin redness Head and neck – taste alterations, dry mouth, mucositis, skin redness Brain – hair loss, scalp redness Brain – hair loss, scalp redness Pelvis – diarrhea, cramping, urinary frequency, vaginal irritation Pelvis – diarrhea, cramping, urinary frequency, vaginal irritation Prostate – impotence, urinary symptoms, diarrhea Prostate – impotence, urinary symptoms, diarrhea Fatigue is often seen when large areas are irradiated Fatigue is often seen when large areas are irradiated Modern radiation therapy techniques have decreased these side effects significantly Unlike the systemic side effects from chemotherapy, radiation therapy usually only impacts the area that received radiation

12. Palliative Radiation Therapy Commonly used to relieve pain from bone cancers Commonly used to relieve pain from bone cancers ~ 50 percent of patients receive total relief from their pain ~ 50 percent of patients receive total relief from their pain 80 to 90 percent of patients will derive some relief 80 to 90 percent of patients will derive some relief Other palliative uses: Other palliative uses: Spinal cord compression Spinal cord compression Vascular compression, e.g., superior vena cava syndrome Vascular compression, e.g., superior vena cava syndrome Bronchial obstruction Bronchial obstruction Bleeding from gastrointestinal or gynecologic tumors Bleeding from gastrointestinal or gynecologic tumors Esophageal obstruction Esophageal obstruction Radiation is effective therapy for relief of bone pain from cancer

13. The Radiation Oncology Team Radiation Oncologist Radiation Oncologist The doctor who prescribes and oversees the radiation therapy treatments The doctor who prescribes and oversees the radiation therapy treatments Medical Physicist Medical Physicist Ensures that treatment plans are properly tailored for each patient, and is responsible for the calibration and accuracy of treatment equipment Ensures that treatment plans are properly tailored for each patient, and is responsible for the calibration and accuracy of treatment equipment Dosimetrist Dosimetrist Works with the radiation oncologist and medical physicist to calculate the proper dose of radiation given to the tumor Works with the radiation oncologist and medical physicist to calculate the proper dose of radiation given to the tumor Radiation Therapist Radiation Therapist Administers the daily radiation under the doctor’s prescription and supervision Administers the daily radiation under the doctor’s prescription and supervision Radiation Oncology Nurse Radiation Oncology Nurse Interacts with the patient and family at the time of consultation, throughout the treatment process and during follow-up care Interacts with the patient and family at the time of consultation, throughout the treatment process and during follow-up care

14. The Treatment Process Referral Referral Consultation Consultation Simulation Simulation Treatment Planning Treatment Planning Quality Assurance Quality Assurance

15. Referral Tissue diagnosis has been established Tissue diagnosis has been established Referring physician reviews potential treatment options with patient Referring physician reviews potential treatment options with patient Treatment options may include radiation therapy, surgery, chemotherapy or a combination Treatment options may include radiation therapy, surgery, chemotherapy or a combination It is important for a referring physician to discuss all possible treatment options available to the patient

16. Consultation Radiation oncologist determines whether radiation therapy is appropriate Radiation oncologist determines whether radiation therapy is appropriate A treatment plan is developed A treatment plan is developed Care is coordinated with other members of patient’s oncology team Care is coordinated with other members of patient’s oncology team The radiation oncologist will discuss with the patient which type of radiation therapy treatment is best for their type of cancer

17. Simulation Patient is set up in treatment position on a dedicated CT scanner Patient is set up in treatment position on a dedicated CT scanner Immobilization devices may be created to assure patient comfort and daily reproducibility Immobilization devices may be created to assure patient comfort and daily reproducibility Reference marks or “tattoos” may be placed on patient Reference marks or “tattoos” may be placed on patient CT simulation images are often fused with PET or MRI scans for treatment planning CT simulation images are often fused with PET or MRI scans for treatment planning

18. Treatment Planning Physician outlines the target and organs at risk Physician outlines the target and organs at risk Sophisticated software is used to carefully derive an appropriate treatment plan Sophisticated software is used to carefully derive an appropriate treatment plan Computerized algorithms enable the treatment plan to spare as much healthy tissue as possible Computerized algorithms enable the treatment plan to spare as much healthy tissue as possible Medical physicist checks the chart and dose calculations Medical physicist checks the chart and dose calculations Radiation oncologist reviews and approves final plan Radiation oncologist reviews and approves final plan Radiation oncologists work with medical physicists and dosimetrists to create the optimal treatment plan for each individualized patient

19. Safety and Quality Assurance Each radiation therapy treatment plan goes through many safety checks Each radiation therapy treatment plan goes through many safety checks The medical physicist checks the calibration of the linear accelerator on a regular basis to assure the correct dose is being delivered The medical physicist checks the calibration of the linear accelerator on a regular basis to assure the correct dose is being delivered The radiation oncologist, along with the dosimetrist and medical physicist go through a rigorous multi-step QA process to be sure the plan can be safely delivered The radiation oncologist, along with the dosimetrist and medical physicist go through a rigorous multi-step QA process to be sure the plan can be safely delivered QA checks are done by the radiation therapist daily to ensure that each patient is receiving the treatment that was prescribed for them QA checks are done by the radiation therapist daily to ensure that each patient is receiving the treatment that was prescribed for them

20. Delivery of Radiation Therapy External beam radiation therapy typically delivers radiation using a linear accelerator Internal radiation therapy, called brachytherapy, involves placing radioactive sources into or near the tumor The modern unit of radiation is the Gray (Gy), traditionally called the rad 1Gy = 100 centigray (cGy) 1cGy = 1 rad The type of treatment used will depend on the location, size and type of cancer.

21. Types of External Beam Radiation Therapy Two-dimensional radiation therapy Two-dimensional radiation therapy Three-dimensional conformal radiation therapy (3-D CRT) Three-dimensional conformal radiation therapy (3-D CRT) Intensity modulated radiation therapy (IMRT) Intensity modulated radiation therapy (IMRT) Image Guided Radiation Therapy (IGRT) Image Guided Radiation Therapy (IGRT) Intraoperative Radiation Therapy (IORT) Intraoperative Radiation Therapy (IORT) Stereotactic Radiotherapy (SRS/SBRT) Stereotactic Radiotherapy (SRS/SBRT) Particle Beam Therapy Particle Beam Therapy

22. Three-Dimensional Conformal Radiation Therapy (3-D CRT) Uses CT, PET or MRI scans to create a 3-D picture of the tumor and surrounding anatomy Uses CT, PET or MRI scans to create a 3-D picture of the tumor and surrounding anatomy Improved precision, decreased normal tissue damage Improved precision, decreased normal tissue damage

23. Intensity Modulated Radiation Therapy (IMRT) A highly sophisticated form of 3-D CRT allowing radiation to be shaped more exactly to fit the tumor A highly sophisticated form of 3-D CRT allowing radiation to be shaped more exactly to fit the tumor Radiation is broken into many “beamlets,” the intensity of each can be adjusted individually Radiation is broken into many “beamlets,” the intensity of each can be adjusted individually IMRT allows higher doses of radition to be delivered to the tumor while sparing more healthy surrounding tissue IMRT allows higher doses of radition to be delivered to the tumor while sparing more healthy surrounding tissue

24. Image Guidance For patients treated with 3-D or IMRT Physicians use frequent imaging of the tumor, bony anatomy or implanted fiducial markers for daily set-up accuracy Imaging performed using CT scans, high quality X-rays, MRI or ultrasound Motion of tumors can be tracked to maximize tumor coverage and minimize dose to normal tissues Fiducial markers in prostate visualized and aligned

25. Stereotactic Radiosurgery (SRS) SRS is a specialized type of external beam radiation that uses focused radiation beams targeting a well-defined tumor SRS is a specialized type of external beam radiation that uses focused radiation beams targeting a well-defined tumor SRS relies on detailed imaging, 3-D treatment planning and complex immobilization for precise treatment set-up to deliver the dose with extreme accuracy SRS relies on detailed imaging, 3-D treatment planning and complex immobilization for precise treatment set-up to deliver the dose with extreme accuracy Used on the brain or spine Used on the brain or spine Typically delivered in a single treatment or fraction Typically delivered in a single treatment or fraction

26. Stereotactic Body Radiotherapy (SBRT) SBRT refers to stereotactic radiation treatments in 1-5 fractions on specialized linear accelerators SBRT refers to stereotactic radiation treatments in 1-5 fractions on specialized linear accelerators Uses sophisticated imaging, treatment planning and immobilization techniques Uses sophisticated imaging, treatment planning and immobilization techniques Respiratory gating may be necessary for motions management, e.g., lung tumors Respiratory gating may be necessary for motions management, e.g., lung tumors SBRT is used for a number of sites: spine, lung, liver, brain, adrenals, pancreas SBRT is used for a number of sites: spine, lung, liver, brain, adrenals, pancreas Data maturing for sites such as prostate Data maturing for sites such as prostate

27. Proton Beam Therapy Protons are charged particles that deposit most of their energy at a given depth, minimizing risk to tissues beyond that point Protons are charged particles that deposit most of their energy at a given depth, minimizing risk to tissues beyond that point Allows for highly specific targeting of tumors located near critical structures Allows for highly specific targeting of tumors located near critical structures Increasingly available in the U.S. Increasingly available in the U.S. Most commonly used in treatment of pediatric, CNS and intraocular malignancies Most commonly used in treatment of pediatric, CNS and intraocular malignancies Data maturing for use in other tumor sites Data maturing for use in other tumor sites Proton Gantry Source: Mevion

28. Types of Internal Radiation Therapy Intracavitary implants Intracavitary implants Radioactive sources are placed in a cavity near the tumor (breast, cervix, uterine) Radioactive sources are placed in a cavity near the tumor (breast, cervix, uterine) Interstitial implants Interstitial implants Sources placed directly into the tissue (prostate, vagina) Sources placed directly into the tissue (prostate, vagina) Intra-operative implants Intra-operative implants Surface applicator is in direct contact with the surgical tumor bed Surface applicator is in direct contact with the surgical tumor bed

29. Brachytherapy Radioactive sources are implanted into the tumor or surrounding tissue Radioactive sources are implanted into the tumor or surrounding tissue 125 I, 103 Pd, 192 Ir, 137 Cs 125 I, 103 Pd, 192 Ir, 137 Cs Purpose is to deliver high doses of radiation to the desired target while minimizing the dose to surrounding normal tissues Purpose is to deliver high doses of radiation to the desired target while minimizing the dose to surrounding normal tissues Radioactive seeds for a permanent prostate implant, an example of low-dose-rate brachytherapy.

30. Brachytherapy Dose Rate Low-Dose-Rate (LDR) Low-Dose-Rate (LDR) Radiation delivered over days and months Radiation delivered over days and months Prostate, breast, head and neck, and gynecologic cancers may be treated with LDR brachytherapy Prostate, breast, head and neck, and gynecologic cancers may be treated with LDR brachytherapy High-Dose-Rate (HDR) High-Dose-Rate (HDR) High energy source delivers the dose in a matter of minutes rather than days High energy source delivers the dose in a matter of minutes rather than days Gynecologic, breast, head and neck, lung, skin and some prostate implants may use HDR brachytherapy Gynecologic, breast, head and neck, lung, skin and some prostate implants may use HDR brachytherapy LDR prostate implant

31. Permanent vs. Temporary Implants Permanent implants release small amounts of radiation over a period of several months Permanent implants release small amounts of radiation over a period of several months Examples include low-dose-rate prostate implants (“seeds”) Examples include low-dose-rate prostate implants (“seeds”) Patients receiving permanent implants may be minimally radioactive and should avoid close contact with children or pregnant women Patients receiving permanent implants may be minimally radioactive and should avoid close contact with children or pregnant women Temporary implants are left in the body for several hours to several days Temporary implants are left in the body for several hours to several days Patient may require hospitalization during the implant depending on the treatment site Patient may require hospitalization during the implant depending on the treatment site Examples include low-dose-rate GYN implants and high-dose-rate prostate or breast implants Examples include low-dose-rate GYN implants and high-dose-rate prostate or breast implants

32. Intraoperative Radiation Therapy (IORT) IORT delivers a concentrated dose of radiation therapy to a tumor bed during surgery IORT delivers a concentrated dose of radiation therapy to a tumor bed during surgery Advantages Advantages Decrease volume of tissue in boost field Decrease volume of tissue in boost field Ability to exclude part or all of dose-limiting normal structures Ability to exclude part or all of dose-limiting normal structures Increase the effective dose Increase the effective dose Multiple sites Multiple sites Pancreas, stomach, lung, esophagus, colorectal, sarcomas, pediatric tumors, bladder, kidney, gyn Pancreas, stomach, lung, esophagus, colorectal, sarcomas, pediatric tumors, bladder, kidney, gyn Several recent trials have shown efficacy for breast cancer Several recent trials have shown efficacy for breast cancer

33. Systemic Radiation Therapy Radiation can also be delivered by an injection. Radiation can also be delivered by an injection. Metastron ( 89 Strontium), Quadramet ( 153 Samarium) and Xofigo ( 223 Radium) are radioactive isotopes absorbed primarily by cancer cells Metastron ( 89 Strontium), Quadramet ( 153 Samarium) and Xofigo ( 223 Radium) are radioactive isotopes absorbed primarily by cancer cells Used for treating bone metastases Used for treating bone metastases Radioactive isotopes may be attached to an antibody targeted at tumor cells Radioactive isotopes may be attached to an antibody targeted at tumor cells Zevalin, Bexxar for Lymphomas Zevalin, Bexxar for Lymphomas Radioactive “beads” may be used to treat primary or metastatic liver cancer Radioactive “beads” may be used to treat primary or metastatic liver cancer Y 90 -Microspheres Y 90 -Microspheres

34. Public Awareness of Radiation Therapy  Patients report going to friends and family and their referring physician to get cancer treatment information

35. Summary Radiation therapy is a well established modality for the treatment of numerous malignancies Radiation therapy is a well established modality for the treatment of numerous malignancies Radiation oncologists are specialists trained to treat cancer with a variety of forms of radiation Radiation oncologists are specialists trained to treat cancer with a variety of forms of radiation Treatment delivery is safe, quick and painless Treatment delivery is safe, quick and painless

36. For More Information… The American Society for Radiation Oncology (ASTRO) can provide information on radiation therapy The American Society for Radiation Oncology (ASTRO) can provide information on radiation therapy Visit www.rtanswers.org to view information on how radiation therapy works to treat various cancers Visit www.rtanswers.org to view information on how radiation therapy works to treat various cancerswww.rtanswers.org